Rheumatoid arthritis (RA) is a chronic, debilitating multisystem disease affecting nearly two million persons in the United States alone. The incidence of RA in men under the age of forty-five is less than that reported in women, however the incidence approaches that of women in older age groups of men. This increased incidence in males coincides with decreasing levels of sex hormones. A hypogonadic condition characterized by low serum testosterone has been previously described in male RA patients compared with age-matched controls with osteoarthritis, ankylosing spondylitis and healthy controls. Patients with RA have significant disability with decreased function over time. Androgens have the potential to increase nitrogen retention, lean body mass, strength, and body weight which could slow the decline in function. Patients with RA also have both local and systemic forms of osteoporosis. There is evidence that androgens may stimulate the proliferation and differentiation of osteoblasts and osteoblast-like cells in vitro which may help reduce the rate of bone loss in RA. Previous studies in both animal models and humans seem to suggest that androgen administration may be beneficial in a number of autoimmune diseases including RA. In this study, we will examine the role of transdermal testosterone versus placebo in male patients with RA over a two-year period. Specifically, we will examine (1) the effect of testosterone on lean body mass and muscle strength with the use of whole body dual xray absorptiometry (DXA) scan and muscle strength testing, (2) the effect of testosterone on bone mineral density by DXA scan of the spine and hip, and (3) the effect of testosterone on disease specific measures of quality of life with validated instruments for quality of life. Additionally, measure of disease activity and side effects will also be assessed. The results of this study will (1) help to define the role of androgen administration and its effects on function through assessment of muscle mass and strength, (2) explore the potential benefits of testosterone therapy on bone mineral density in patients with both localized and systemic forms of osteoporosis, (3) define changes in quality of life in patients with RA treated with androgen, and (4) help to define the potential role of androgen therapy in other systemic illnesses where muscle wasting has a profound impact on quality of life (e.g. both inflammatory and non-inflammatory muscle disease). In addition, this K-23 grant will provide opportunity for further career development through mentorship provided by an committee with multiple areas of expertise and formal education in the areas of clinical research design and conduct, outcome assessment development and analysis, and clinical trial analysis.